Exploiting Aneuploidy in NF1-MPNST: Prognostication and Understanding Pathogenesis
Abstract
Neurofibromatosis type 1 (NF1) is a common cancer predisposition syndrome, affecting 1 in 3,000 individuals worldwide. Our group has defined the molecular heterogeneity of MPNST using sequencing of patient-derived xenografts (PDX) models. We have demonstrated that MPNST exhibit a high degree of aneuploidy, while their benign PN counterparts are usually diploid. Additionally, we showed that MPNST uniformly demonstrate gains involving the long arm of chromosome 8 (Chr8q), where several cancer-related genes are located. These genes are highly expressed in primary MPNST, and are maintained in their corresponding PDX. Pathway analyses suggest that Chr8q gain leads to increased expression of genes involved in diverse processes including connective tissue development, stem cell maintenance, and ribosomal RNA processing offering potential mechanisms for Chr8q cancer promotion. Moreover, leveraging The Cancer Genome Atlas (TCGA) database, we found that Chr8q gain was associated with reduced overall survival (OS) in patients with soft tissue sarcomas, which may explain the poor prognosis of MPNST. Based on these observations, we hypothesize that Chr8q gain is a critical driver of MPNST progression, and functions by increasing the expression of a set of cancer genes responsible for the tumor growth and progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1219025
Entities
People
- Angela Hirbe
Organizations
- Washington University in St. Louis